Bone Metastases

Metastasis is considered as the ultimate step in the stage-wise progression of tumor. Occurrence of metastases can be regarded as either increased disease aggression or failure to respond to the treatment provided. Metastases can be defined as the spread of tumor cells to areas via blood vessels or lymphatic channels.

Who are susceptible for bone metastases?

Bone is the third most common site of metastasis after lungs and liver. It frequently involves individuals who have aggressive disseminated cancer disease or elderly individuals. 80% of patients with disseminated cancer have skeletal metastases. Less than 50% experience bone symptoms and less than 10% have pathological fractures. Two-thirds of pathological fractures in the appendicular skeleton involve the femur and the rest involve the humerus.

How does an individual with specific cancer get metastases?

Tumor cells grow rapidly than normal cells. Certain factors in our body help the tumor cells produce new blood circulation thereby enhancing rapid growth and spread. The so called “Ligands” bind to specific receptors and alter the balance in cell signals. Bone is rich in such factors like, TGF (transforming growth factors), PDGF (platelet derived growth factors), TNF (tumor necrosis factor), parathyroid hormone-related protein (PTHrP), RANK-L (receptor activator of nuclear factor kappa B ligand) and osteoprotegerin. These factors are capable of supporting tumor growth which may account for the high incidence of skeletal metastases in certain types of cancers. RANK-L stimulates bone resorption whereas osteoprotegerin blocks resorption. The ratio between the two influences bone remodeling and results in ‘vicious cycle’ of osteoclast activation leading to areas of weakened bone.

What are the bones affected by metastases?

Most metastases affect axial skeleton (includes vertebral column, pelvis, ribs and sacrum) which contain the red marrow. In the body, spine is the commonest site followed by femur, humerus and pelvis.

What cancers spread to the bones?

Carcinoma is the most common type of cancer to metastasize to the skeleton followed by myeloma and lymphoma. Among the carcinomas, most common are carcinomas of breast and lung (nearly 80 %), kidney, prostate and thyroid.

Does the survival change with occurrence or identification of metastases?

The mean survival time of patients with metastatic breast cancer, myeloma and lymphoma is 28 months following surgical intervention. The mean survival time of prostate and renal metastases is 20 months and that of lung metastases is 6 months.

How is metastases identified?

Bone metastases typically affect multiple sites. They cause pain, tenderness and worsening disability. These symptoms are predominantly due to osteoclastic bone resorption. In any patient with known cancer, bone pain is assumed to be due to metastases until proved otherwise. These individual undergoes a series of tests to identify the primary disease and the metastases as following:

Blood Investigations

  • Complete Hemogram
  • ESR
  • CRP
  • Serum Calcium, Phosphorous
  • Alkaline Phosphatase
  • Serum Uric acid
  • Renal and Liver Function tests
  • Enzymatic assays specific to primary cancer

Imaging – to determine local extent.

  • Plain radiographs (X-ray): X-ray of the Chest and whole region involved is performed. It provides details about bone destruction or any impending pathological fracture. Lesions may be seen as sclerotic (bright and dense), lytic (hazy and dark) and sometimes mixed. There may be presence of multiple lesions along the length of the bone or spine, termed as “skip lesions”.

  • Computed Tomography (CT) Scan: Produces excellent soft tissue and contrast resolution which shows both sclerotic and lytic lesions. Useful in spinal metastases.

  • Magnetic Resonance Imaging (MRI): Helps to distinguish metastases from infections in the spine.

  • Bone Scan: Sensitive method for detection but not very specific. Useful to detect attention to areas of skeleton that require further work up.
  • PET scan: To assess systemic disease load or staging. Can also be used to identify primary source in case of patient presenting with isolated lesion without known cause or presence of cancer.

 

Biopsy- To confirm the lesion

  • Essential when primary is unknown or individual presents with a single suspected metastatic lesion.
  • Not necessary when the primary cancer is identified or there are multiple lesions suspected as secondary.
  • Bone lesions can be accessed by jamshedi needle, performed in out-patient clinic.
  • Spinal lesions can be dealt with by needle biopsy under CT guidance or transpedicular biopsy.

What is Unknown Primary? How to identify the main cause of cancer or metastases?

Individuals over the age of 30 years may present with symptoms not usually depicting cancer. On single, multiple or repeated investigations, single or multiple lesions may be noted which may suggest metastases or secondary lesions. The aim is to identify the primary cancer by the following tests:

  • Thorough clinical examination
  • Complete Hemogram
  • Serum electrophoresis
  • Liver function tests
  • Renal function tests
  • Serum uric acid, Calcium & Phosphorous
  • Lactate dehydrogenase, Prostate specific antigen (PSA), Acid phosphatase, Ca-125 and other specific enzymatic markers
  • Chest x-ray
  • Ultrasound abdomen and pelvis
  • CT thorax and abdomen

What are the outcomes or complications of bone metastases?

Bone metastases can result in variety of symptoms and clinical problems which need to be either managed conservatively or tackled as medical emergency.

  • Pain
  • Pathological fracture (Mirel’s criteria)
  • Spinal cord compression (medical emergency)
  • Spinal instability Cranial nerve palsies (skull base metastases)
  • Hypocalcaemia(weakness, lethargy, confusion, polyuria, constipation)
  • Bone marrow suppression

How are bone metastases treated?

Treatment of individuals with bone metastases are customized and based on the following factors:

  1. Primary cancer histology
  2. Stage of primary cancer prior to metastases
  3. Symptoms and clinical signs
  4. Prognosis and anticipated survival
  5. Bone/ Bones involved
  6. Extent of Metastases (Single or Multiple)
  7. Functional status of the patient
  8. Scope for adjuvant therapy (Chemotherapy & Radiotherapy)

How are individuals with single metastases treated?

Single lesions, well documented after extensive survey and biopsy are treated with curative intent. When found in long bones or extremities, they are customized based on functional demands of individual.  Below are different scenarios and approach towards them:

  1. A 55 year lady who has been operated for breast carcinoma 6 years prior has presented with pain in the hip region since 2 months. Routine tests are performed followed by PET CT NAF/FDG and a single lesion in proximal femur is identified. This portrays a good prognosis if metastases is approached with curative intent. Hence, she is either treated with extended curettage-cementing & intramedullary nailing or excision of proximal femur and tumor endoprosthesis. A tumor endoprosthesis is favored in this age group and bone involved due to the advantage of rapid return of functional status and independence. If this individual had presented with pathological fracture, the ideal treatment would also be tumor endoprosthetic reconstruction to aid in mobilization.
  2. Similarly, a 60 year gentleman who is being treated for lung cancer presented with sudden pain in arm. On investigations, a pathological fracture of humerus bone is noted. This portrays a fair or poor prognosis with reduced long term survival. The aim is to relieve pain and allow daily functional activities. He is treated with extended curettage-cementing and intramedullary nailing which relieves the pain and also stabilizes the fractured bone.
  3. 66 year old gentleman presented with complains of back pain. On investigations, a single lesion was noted in the Lumbar 2 vertebrae with fracture. Thorough workup is done identify the primary cancer and was noted as prostate cancer. Relevant treatment was initiated for prostate cancer, followed by aim to treat pain and subsequently mobilize. Hence, kyphoplasty (balloon cement injection to stabilize and strengthen the vertebra) was performed.
  4. 48 year lady presented with pain in hip region for 1 month. She was treated for carcinoma of breast 3 years ago. On investigations, a solitary lesion was identified in acetabulum are of hip joint. The lesion appears to be localized and not affecting the functional status, hence a surgical intervention would be morbid. This lesion is treated by External beam Radiotherapy which relieves pain and often cures the lesion.
Thyroid Cancer Metastases to Bone
Pathological fracture secondary to breast metastases, treated with tumour endoprosthesis

What are the metastatic cancers currently treated with curative intent?

Metastases from primary cancers of breast, thyroid and kidney can be treated with extensive procedures to prolong survival and improve function in present scenario. If all the factors mentioned earlier provide an estimated survival of greater than 6 months, it is preferable to treat with curative intent to improve the functional status and quality of life.

Bone metasases secondary to renal cell carcinoma

 

How are individuals with multiple metastases treated?

Multiple metastases when identified portray poor prognosis and reduce the chances of long term survival. Supportive therapy or Palliative care is mainstay of treatment in these individuals. These include multi-disciplinary approach involving the musculoskeletal oncosurgeon, medical oncologist, radiation oncologist, pain and palliative specialist, social worker and physiotherapist. Each scenario is discussed in multi-disciplinary meeting similar to sarcoma and appropriate, suitable, customized treatment is provided.

How is Radiotherapy beneficial in bone metastases?

Radiotherapy can be provided with either “Curative or Palliative Intent” for bone metastases.

Various modalities are Local external beam radiotherapy (single lesion), Hemi body radiotherapy (multiple lesions) and as radioisotopes.

The response of bone metastases is dependent on the primary tumor, extent of bone involvement and functional-psychosocial status of the individual. Individuals may experience transient or permanent pain relief within a weeks of radiotherapy. Radiotherapy is associated with complications related to gastrointestinal system and bone marrow toxicity.

Radionuclide isotopes have also been used in to treat bone metastases, especially from thyroid and prostate (strontium, radioactive iodine). The isotopes reach the metastases and provide palliative pain relief.

How are bisphosphonates beneficial in bone metastases?

Bisphosphonates are mainly used for palliative intent, targeting the osteoclastic bone resorption.

  • Strengthening of a weakened bone, preventing pathological fracture
  • Long term relief of bone pain.
  • Hypercalcemia of malignancy

There are also reports suggesting the delay in appearance or preventing worsening of bone metastases in patient with primary cancer. However, they do not play a role in improving the long term survival.

Most commonly used bisphosphonate is Zoledronic acid in dose of 4 mg per year, intravenously. Side effects include gastro-intestinal disturbances, fever, dizziness, weakness and fatigue.